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In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.
Modern implementations of driver assistance systems are evolving from a pure driver assistance to a independently acting automation system. Still these systems are not covering the full vehicle usage range, also called operational design domain, which require the human driver as fall-back mechanism. Transition of control and potential minimum risk manoeuvres are currently research topics and will bridge the gap until full autonomous vehicles are available. The authors showed in a demonstration that the transition of control mechanisms can be further improved by usage of communication technology. Receiving the incident type and position information by usage of standardised vehicle to everything (V2X) messages can improve the driver safety and comfort level. The connected and automated vehicle’s software framework can take this information to plan areas where the driver should take back control by initiating a transition of control which can be followed by a minimum risk manoeuvre in case of an unresponsive driver. This transition of control has been implemented in a test vehicle and was presented to the public during the IEEE IV2022 (IEEE Intelligent Vehicle Symposium) in Aachen, Germany.
Density Operator
(2009)
Density reduction effects on the production of [11C]CO2 in Nb-body targets on a medical cyclotron
(2023)
Medical isotope production of 11C is commonly performed in gaseous targets. The power deposition of the proton beam during the irradiation decreases the target density due to thermodynamic mixing and can cause an increase of penetration depth and divergence of the proton beam. In order to investigate the difference how the target-body length influences the operation conditions and the production yield, a 12 cm and a 22 cm Nb-target body containing N2/O2 gas were irradiated using a 13 MeV proton cyclotron. It was found that the density reduction has a large influence on the pressure rise during irradiation and the achievable radioactive yield. The saturation activity of [11C]CO2 for the long target (0.083 Ci/μA) is about 10% higher than in the short target geometry (0.075 Ci/μA).
With the variety of toothbrushes on the market, the question arises, which toothbrush is best suited to maintain oral health? This thematic review focuses first on plaque formation mechanisms and then on the plaque removal effectiveness of ultrasonic toothbrushes and their potential in preventing oral diseases like periodontitis, gingivitis, and caries. We overviewed the physical effects that occurred during brushing and tried to address the question of whether ultrasonic toothbrushes effectively reduced the microbial burden by increasing the hydrodynamic forces. The results of published studies show that electric toothbrushes, which combine ultrasonic and sonic (or acoustic and mechanic) actions, may have the most promising effect on good oral health. Existing ultrasonic/sonic toothbrush models do not significantly differ regarding the removal of dental biofilm and the reduction of gingival inflammation compared with other electrically powered toothbrushes, whereas the manual toothbrushes show a lower effectiveness.
Purpose
To design and evaluate a four-channel cardiac transceiver coil array for functional cardiac imaging at 7T.
Materials and Methods
A four-element cardiac transceiver surface coil array was developed with two rectangular loops mounted on an anterior former and two rectangular loops on a posterior former. specific absorption rate (SAR) simulations were performed and a Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-1 calibration method was applied prior to obtain 2D FLASH CINE (mSENSE, R = 2) images from nine healthy volunteers with a spatial resolution of up to 1 × 1 × 2.5 mm3.
Results
Tuning and matching was found to be better than 10 dB for all subjects. The decoupling (S21) was measured to be >18 dB between neighboring loops, >20 dB for opposite loops, and >30 dB for other loop combinations. SAR values were well within the limits provided by the IEC. Imaging provided clinically acceptable signal homogeneity with an excellent blood-myocardium contrast applying the Burn:x-wiley:10531807:media:JMRI22451:tex2gif-stack-2 calibration approach.
Conclusion
A four-channel cardiac transceiver coil array for 7T was built, allowing for cardiac imaging with clinically acceptable signal homogeneity and an excellent blood-myocardium contrast. Minor anatomic structures, such as pericardium, mitral, and tricuspid valves and their apparatus, as well as trabeculae, were accurately delineated.
Design and Development of a Hot S-Parameter Measurement System for Plasma and Magnetron Applications
(2020)
This paper presents the design, development and calibration procedures of a novel hot S-parameter measurement system for plasma and magnetron applications with power level up to 6 kW. Based on a vector network analyzer, a power amplifier and two directional couplers, the input matching hotS 11 and transmission hotS 21 of the device under test are measured at 2.45 GHz center frequency and 300MHz bandwidth, while the device is driven by the magnetron. This measurement system opens a new horizon to develop many new industrial applications such as microwave plasma jets, dryer systems, dryers and so forth. Furthermore, the developing, controlling and monitoring a 2kW 2.45GHz plasma jet and a dryer system using the measurement system are presented and explained.
Design and Development of a Novel Self-Igniting Microwave Plasma Jet for Industrial Applications
(2019)
Design and implementation aspects of a 3D reconstruction algorithm for the Jülich TierPET system
(1997)
Design and initial performance of PlanTIS: a high-resolution positron emission tomograph for plants
(2010)
Positron emitters such as 11C, 13N and 18F and their labelled compounds are widely used in clinical diagnosis and animal studies, but can also be used to study metabolic and physiological functions in plants dynamically and in vivo. A very particular tracer molecule is 11CO2 since it can be applied to a leaf as a gas. We have developed a Plant Tomographic Imaging System (PlanTIS), a high-resolution PET scanner for plant studies. Detectors, front-end electronics and data acquisition architecture of the scanner are based on the ClearPET™ system. The detectors consist of LSO and LuYAP crystals in phoswich configuration which are coupled to position-sensitive photomultiplier tubes. Signals are continuously sampled by free running ADCs, and data are stored in a list mode format. The detectors are arranged in a horizontal plane to allow the plants to be measured in the natural upright position. Two groups of four detector modules stand face-to-face and rotate around the field-of-view. This special system geometry requires dedicated image reconstruction and normalization procedures. We present the initial performance of the detector system and first phantom and plant measurements.
Producing fresh water from saline water has become one of the most difficult challenges to overcome especially with the high demand and shortage of fresh water. In this context, as part of a collaboration with Germany, the authors propose a design and implementation of a pilot multi-stage solar desalination system (MSD), remotely controlled, at Douar Al Hamri in the rural town of Boughriba in the province of Berkane, Morocco. More specifically, they present their contribution on the remote control and supervision system, which makes the functioning of the MSD system reliable and guarantees the production of drinking water for the population of Douar. The results obtained show that the electronic cards and computer communication software implemented allow the acquisition of all electrical (currents, voltages, powers, yields), thermal (temperatures of each stage), and meteorological (irradiance and ambient temperature), remote control and maintenance (switching on, off, data transfer). By comparing with the literature carried out in the field of solar energy, the authors conclude that the MSD and electronic desalination systems realized during this work represent a contribution in terms of the reliability and durability of providing drinking water in rural and urban areas.
The so-called "compound solar sail", also known as "Solar Photon Thruster" (SPT), holds the potential of providing significant performance advantages over the flat solar sail. Previous SPT design concepts, however, do not consider shadowing effects and multiple reflections of highly concentrated solar radiation that would inevitably destroy the gossamer sail film. In this paper, we propose a novel advanced SPT (ASPT) design concept that does not suffer from these oversimplifications. We present the equations that describe the thrust force acting on such a sail system and compare its performance with respect to the conventional flat solar sail.
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Design of a Measurement Setup for the Impedance of Low-Resistance Plate-Conductors in the RF-Range
(2006)
The maintenance of wind turbines is of growing importance considering the transition to renewable energy. This paper presents a multi-robot-approach for automated wind turbine maintenance including a novel climbing robot. Currently, wind turbine maintenance remains a manual task, which is monotonous, dangerous, and also physically demanding due to the large scale of wind turbines. Technical climbers are required to work at significant heights, even in bad weather conditions. Furthermore, a skilled labor force with sufficient knowledge in repairing fiber composite material is rare. Autonomous mobile systems enable the digitization of the maintenance process. They can be designed for weather-independent operations. This work contributes to the development and experimental validation of a maintenance system consisting of multiple robotic platforms for a variety of tasks, such as wind turbine tower and rotor blade service. In this work, multicopters with vision and LiDAR sensors for global inspection are used to guide slower climbing robots. Light-weight magnetic climbers with surface contact were used to analyze structure parts with non-destructive inspection methods and to locally repair smaller defects. Localization was enabled by adapting odometry for conical-shaped surfaces considering additional navigation sensors. Magnets were suitable for steel towers to clamp onto the surface. A friction-based climbing ring robot (SMART— Scanning, Monitoring, Analyzing, Repair and Transportation) completed the set-up for higher payload. The maintenance period could be extended by using weather-proofed maintenance robots. The multi-robot-system was running the Robot Operating System (ROS). Additionally, first steps towards machine learning would enable maintenance staff to use pattern classification for fault diagnosis in order to operate safely from the ground in the future.
Design of enzyme reactors as chromatographic columns for racemic resolution of amino acid esters
(1989)
Within the Crystal Clear Collaboration four centres are developing 2nd generation high performance small animal PET scanners for different kinds of animals and medical applications. The first prototypes are PMT-based systems including depth of interaction (DOI) detection by using a phoswich layer of LSO and LuYAP. The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in FOVs caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN) was used. The simulations have shown that all PMT designs with one-to-one coupling of crystals have a very nonlinear axial sensitivity profile. By shifting every other PMT 1/4 of a PMT length in axial direction the sampling of the FOVs became more homogeneous. At an energy threshold of 350keV the regression coefficient increases from 0.818 for the non-shifted to 0.993 for the shifted design. Simulations of a point source centred in the FOV (threshold: 350keV) resulted in sensitivities of 4.2% for a 4×20PMT (LSO/LuYAP a 10mm) and 3.8% for a 4×16PMT (LSO/LuYAP a 8mm) ring design. The 3D-MLEM reconstruction of a point source shows the enormous improvement of resolution using a crystal double layer with DOI (3.1mm at 40mm from CFOV) instead of a 20mm single layer (11.9mm).
Within the Crystal Clear Collaboration (CCC), four centers are developing second generation high performance small animal positron emission tomography (PET) scanners for different kinds of animals and medical applications. The first prototypes are photomultiplier tube (PMT)-based systems including depth of interaction (DOI) detection by using a phoswich layer of lutetium oxyorthosilicate (LSO) and lutetium yttrium aluminum perovskite (LuYAP). The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in fields of view (FOVs) caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN, Geneva, Switzerland) was used.